Novel biphasic mechanism of the canonical Wnt signalling component PYGO2 promotes cardiomyocyte differentiation from hUC-MSCs.
Novel biphasic mechanism of the canonical Wnt signalling component PYGO2 promotes cardiomyocyte differentiation from hUC-MSCs.
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DOI：
10.1007/s00441-023-03774-6
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发表时间：
2023-07
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
--
作者：
人脐带间充质干细胞（Human umbilical cord-derived mesenchymal stem cells，hUC-MSCs）可用于心肌梗死后的心脏修复。然而，其形成中胚层细胞并分化为心肌细胞的能力的调控机制仍不清楚。在这里，我们建立了从健康脐带中分离的人源性MSC系，并建立了自然状态的细胞模型，以检查hUC-MSC向心肌细胞的分化。采用定量RT-PCR、Western印迹、免疫荧光、流式细胞术、RNA Seq和经典Wnt信号传导抑制剂检测生殖层标记物T和MIXL 1;心脏祖细胞MESP 1、GATA 4和NKX2.5的标志物以及心肌细胞标志物cTnT，以鉴定与PYGO 2相关的分子机制，是经典Wnt信号通路的关键组分，调节心肌细胞样细胞的形成。我们证明PYGO 2通过促进β-catenin早期进入细胞核，通过hUC-MSC依赖的经典Wnt信号传导促进中胚层样细胞的形成及其向心肌细胞的分化。令人惊讶的是，PYGO 2在中晚期阶段没有改变经典Wnt、NOTCH或BMP信号通路的表达。相反，PI 3 K-Akt信号促进hUC-MSC形成并使其分化为心肌样细胞。据我们所知，这是第一项证明PYGO 2使用双相机制促进hUC-MSC形成心肌细胞的研究。在线版本包含补充材料，可通过10.1007/s 00441 -023-03774-6获得。
Human umbilical cord–derived mesenchymal stem cells (hUC-MSCs) are used to regenerate the myocardium during cardiac repair after myocardial infarction. However, the regulatory mechanism underlying their ability to form mesodermal cells and differentiate into cardiomyocytes remains unclear. Here, we established a human-derived MSCs line isolated from healthy umbilical cords and established a cell model of the natural state to examine the differentiation of hUC-MSCs into cardiomyocytes. Quantitative RT-PCR, western blotting, immunofluorescence, flow cytometry, RNA Seq, and inhibitors of canonical Wnt signalling were used to detect the germ-layer markers T and MIXL1; the markers of cardiac progenitor cells MESP1, GATA4, and NKX2.5 and the cardiomyocyte-marker cTnT to identify the molecular mechanism associated with PYGO2, a key component of the canonical Wnt signalling pathway that regulates the formation of cardiomyocyte-like cells. We demonstrated that PYGO2 promotes the formation of mesodermal-like cells and their differentiation into cardiomyocytes through the hUC-MSC-dependent canonical Wnt signalling by promoting the early-stage entry of β-catenin into the nucleus. Surprisingly, PYGO2 did not alter the expression of the canonical-Wnt, NOTCH, or BMP signalling pathways during the middle–late stages. In contrast, PI3K-Akt signalling promoted hUC-MSCs formation and their differentiation into cardiomyocyte-like cells. To the best of our knowledge, this is the first study to demonstrate that PYGO2 uses a biphasic mechanism to promote cardiomyocyte formation from hUC-MSCs. The online version contains supplementary material available at 10.1007/s00441-023-03774-6.
影响因子：
5.7
作者：
Miller, Thomas C. R.;Mieszczanek, Juliusz;Jose Sanchez-Barrena, Maria;Rutherford, Trevor J.;Fiedler, Marc;Bienz, Mariann
通讯作者：
Bienz, Mariann
影响因子：
10.5
作者：
Cantù C;Zimmerli D;Hausmann G;Valenta T;Moor A;Aguet M;Basler K
通讯作者：
Basler K
影响因子：
1.5
作者：
Tang, Min;Yuan, Wuzhou;Bodmer, Rolf;Wu, Xiushan;Ocorr, Karen
通讯作者：
Ocorr, Karen